One of the features of the Fragile X mouse model which is relevant to the human Fragile X syndrome (and autism) is social behavior. Several tests show consistent social behavioral abnormalities in the Fragile X mouse model. With a $140,000 grant from FRAXA Research Foundation in 2012-2013, Dr. Willemsen at Erasmus University used social behavior tests to measure the effectiveness of several drug strategies.
Our research is focused on the development and validation of reliable outcome measures for therapeutic intervention in FXS using behavioral and molecular paradigms in Fmr1 model mice. We have established a reliable behavioral assessment for sociability/social interaction to measure effectiveness of treatment in Fmr1 KO mice using social preference/social novelty task. Chronic administration of an mGluR5 antagonist, AFQ056, was able to rescue sociability deficits in Fmr1 KO mice to levels of wild type animals. Next, we started chronic treatment with baclofen, however, we were not able to observe a rescue of the sociability deficits. We then tested minocycline to measure effectiveness in treatment sociability deficits. In addition, we will determine several biochemical paradigms in synaptoneurosomes from brain tissue of Fmr1 KO mice after behavioral assessment, including GluR1 (AMPA receptor subunit), NR2A (NMDA receptor subunit), STEP, ERK and mGlur5.
